Germicidal piperazine derivatives



3,007,929 GERMICIDAL PIPERAZHNE DERWATW 13$ Edward Joseph Nikawitz, Glen Rock, Nah, assignor to The Givaudan Corporation, New York, NEL, a corbase, in the presence or absence of alcohol or water. The addition of the acids can take place simultaneously, or the acids may be added one at a time, i.e., an unmixed salt is first prepared as above with acid No. 1;

porafion of New Jersey 5 then acid No. 2 is added thereto to form the mixed salt N0 Drawing. Filed Feb 16, 1959, s81, NO of acids No. l and bio. 2 etc. It W11]. be understood 3 Claims, (CL 26h 268) that the number of acid residues which may be contained 1n the mixed salts is limited by the number of amino N This invention relates to novel chemical products, and atoms in the compound. more especially to certain novel alkylamino piperazines The novel products of this invention possess unexpected characterized, in particular, by their germicidal activity. germicidal properties. They may be used, e.g., to ster- My novel substances may be represented by the folilize milk bottles and similar containers for products inlowing formula: tended for human consumption, when dissolved in water OHPOH, in amounts from about 0.01% to about 0.1% by weight 15 of the water. A disinfecting metal cleaner composition R NHCH"CHN can be prepared by dissolving 1 pound of the products HT fl of this invention in 1000 to 10,000 pounds of water or a Where R is C12H25 or C1 41.1% like amount of a 50% solution of water and isopropyl It is understood that, in addition to the bases reprealcoholsented by the foregoing formula, salts made with inorh germlciflial of these Compounds was ganic acids in general or organic aliphatic acids having termmed by the Standard P1161101 Coefiicient not more than 4 carbon atoms in the molecule or organic lest Procadure Dept of Agnculture, Circular 198, aromatic acids having not more than 7 carbon atoms in Dec. 1931) with the Cade-Halvorson plate count modithe molecule are also included in my present invention. t fm (Soap, ug. 10, 17, 1934; Sept. 2o", 1934) to In general the novel products of this invention are obtain the counts, or number of bacteria surviving. made by reacting a l-halododecane or hhalotetradecane Mzcrococcus pyogenes Var. aureus, Salmonella typhosa with more than an equivalent amount of 2 and Escherichia coli were the test organisms used, the ethyl)-piperazine for a few hours at an elevated temperfirst p t g he gram-positive and the latter two ature. After converting the hydrogen halide formed by representmg the g types of ba cteria. The said reaction into salt with alkali and recovering the untemPer atum and Fontact it were and 10 reacted 1-(2-aminoethyl)-piperazine by distillation under Ammus T Slgn means. no growt m the reduced pressure, the desired products are obtained by culture tubes While the W figures repreisgnt the e es r For desirable practical results, it 1s recommendedthat medication tubes at the end of the test pgi A differ from about 2 to about 4 mols of 1-( ence of can be considered as the limits of significant azlne be used mol of the hiflohydmcarbono figures. Counts of more than 5,000 are estimated, as the Temperatures from about 90 to about 150 are plates showed too many colonies to be counted accusatisfactory, although temperatures Within the range Iatehh from a out 1 C- t about are especially rec- 40 Data (averages from several duplicate sets of tests) omrnended. using the procedures as just described are presented in The extent of the reaction is followed by determining th following bl 120,000 in water 140,000 in water 150,000 in water MJZ. st. E.c. Mu. st. Ec. Ma. S.t. E.c.

1-(N-Octyl-2-aminoethyl)piperaz +10,000 1- (N -Decy12-aminoethyl)pipera- .ig figaggynngggggggga; 1: +1000) 000 +1000) 1.tlifffififinzrtansnasnan: 1.left iltdarna aanaaanini +0 +0 +4 +0 +0 1.fifliitliran essentialist perazlne +10, 000 4-(N-Dodeey1-2-aminoethyl)morpholine +10, 000

the amount of ionized halogen in the reaction mixture, in accordance with known procedures.

Among the suitable alkalis which can be used to convert the hydrogen halide into salt may be noted sodium hydroxide and potassium hydroxide.

Salts with inorganic acids, suitable organic acids, and acid-reacting substances such as phenols, are prepared from free bases by the addition of appropriate equivalent amounts of acidic substances, the amount being determined by the number of basic nitrogen atoms to be neutralized.

Mixed salts can be prepared from the free bases or from unmixed salts, i.e., salts with at least one basic nitrogen atom. When free bases are employed, suitable equivalent amounts of two or more acids are added to the 1. Technical I-(N-lauryl-Z-aminoelhyl) piperrzzine Technical lauryl chloride (40.8 g., distilling range: -160/5 mm.) was dropped during one hour into 104.0 g. of 1-(2arninoethyl)piperazine, being agitated and heated to 100105 C. in a flask fitted with a sealed stirrer, a thermometer, a dropping funnel and a reflux condenser. The whole was then stirred and heated at 120 for an additional 5 hours. Absolute ethanol (150 ml.) and a solution of 8 g. of sodium hydroxide in 10 ml. of water were then added at 80 C. After refluxing for 30 minutes, the contents of the flask were agitated for 3 hours at room temperature.

The precipitated salt was filtered OE and the filtrate was freed of the solvent by distillation at slightly reduced pressure. The residue was distilled at a pressure of 3 mm. At 90-150 C., the recovered 1-(2-aminoethyl)piperazine (72.3 g.) distilled over. The fraction, distilling at 150-220 C. was technical 1-(N-laury1-2-aminoethyl)- piperazine. Yield: 48.3 g. (118.4% by weight, based on lauryl chloride). It is a cloudy, yellow oil, soluble in Water and 1% hydrochloric acid. Its solution in 1% sodium hydroxide is very turbid.

Analysis.-Calcd. for C H N C, 72.8%; H, 13.1%; N, 14.1%. Found: C, 72.8%; H, 12.8%; N, 14.4%.

EXAMPLE II 2. Pure 1-(N-dodecyl-Z-aminoethyl)piperazine This compound was prepared according to the method of Example I. Pure l-chlorododecane (40.8 g.) was used instead of technical lauryl chloride. The fraction with a distilling range of 192198 C. at 3 mm. was pure 1-(N-dodecyl-Z-aminoethyl)piperazine. Yield: 33.5 g. (82% by weight, based on chlorododecane). It is a cloudy, yellow oil, soluble in water and 1% hydrochloric acid. Its solution in 1% sodium hydroxide is slightly hazy and viscous. All solutions foam.

Analysis.-Calcd. for C H N C, 72.8%; H, 13.1%; N, 14.1%. Found: C, 72.2%, n 1.4737; H, 12.9%; N, 143%.

Additional 14.1 g. of the compound, distilling at 198 215 C. at 3 mm., had the same refractive index.

4 EXAMPLE III 3. 1-(N-tetradecyl-Z-aminoethyl) piperazine 1-chlorotetradecane (27.8 g.), 1-(2-aminoethyl)-piperazine (52 g.), sodium hydroxide (4 g. in 5 ml. of water) and ethanol ml.) were brought to reaction as described in Example I. The fraction distilling at -165 C. at 5 mm. was pure 1-(N tetradecyl-2-arninoethyl)-piperazine. Yield: 15.9 g. (57.2% by Weight, based on l-chlorotetradecane). It is a cloudy, yellow oil. Its 1% solution in water is viscous and does not foam to a great degree. With 1% hydrochloric acid, it forms a clear, foaming solution. Its dispersion in 1% sodium hydroxide is foaming.

Analysis.-Calcd. for C H N C, 73.9%; H, 13.2%; N, 12.9%. Found: C, 74.0%, m 1.4737; H, 12.9%; N, 13.2%.

The products made in accordance with the foregoing specific examples, when incorporated in water to the extent of 0.01% to 0.1% by weight of the water, were effective in sterilizing milk bottles and disinfecting metallic kitchen utensils.

The foregoing illustrates the invention, which, however, is not to be limited thereby, but is to be construed as broadly as permissible in view of the prior art and limited solely by the appended claims.

I claim:

1. A compound having the formula:

CHZCH2 where R is a member selected from the group consisting of dodecyl and tetradecyl; and the hydrochloride of said compound.

2. 1-(N-dodecyl-Z-aminoethyl)-piperazine.

3. 1-(N-tetradecyl-Z-aminoethyl)-piperazine.

References Cited in the file of this patent Hromatka et :al.: Monatshet'te fur Chemie, vol. 82, page 884 (1951). 

1. A COMPOUND HAVING THE FORMULA: 